Inheritance outside DNA

Most people have heard that human inheritance is spelled out in our DNA and activated through our genes. Yet few know anything about epigenetics, a variety of methods that our cells have evolved to transmit heritable changes without changing DNA.

Among other things, epigenetics is crucial to differentiation, the process which makes one cell from another, and thus is at the heart of the mystery of stem cells.

Genomic imprinting is a type of epigenetic change that causes one copy of a particular gene to be turned off, depending on its parental origin. It works largely by altering the methylation patterns"the addition or subtraction of methyl groups"around a gene, but not the DNA sequence itself. These methylation patterns are reprogrammed when passed from generation to generation, carrying instructions related to the parent from whom that copy was inherited but without altering the DNA.

Abnormal methylation patterns in cancerous cells were discovered more than 20 years ago. Yet tumor cells have so many things wrong with them, including methylation abnormalities, that a precise cause-and-effect relationship between cancer and epigenetic alterations has been difficult to pin down, says Andrew Feinberg of the John Hopkins School of Medicine, who has been a pioneer in unraveling the epigenetics of cancer.

Now Feinberg has taken a new look at genomic imprinting, as a cancer-predisposing factor. Feinberg analyzed a common epigenetic alteration—found in 5–10 percent of the general population—that involves the loss of imprinting on an insulin-like growth factor gene called IGF2. Loss of imprinting of IGF2 has been associated statistically with individuals who have personal and familial histories of colorectal cancer. Turning to mice that modeled the loss of IGF2 imprinting, Feinberg found an increase in frequency of tumors in mice who also had mutations in a cancer-associated gene called Apc. In the mutant Apc mice, the loss of IGF2 imprinting seems to particularly affect the behavior of the adult stem cells that continually regenerate the colon in mice. This probably plays a role in the increased risk of colon cancer, says Feinberg.

Spotting epigenetic markers like lost IGF2 in humans could be used in future cancer-prevention strategies. Says Feinberg, “It could be possible to screen for colon cancer risk by looking at the epigenetic changes in colon cells of healthy people.” Source : American Society for Cell Biology